GLASGOW, U.K.— A landmark,
multinational, collaborative stem-cell research project led by Belgium-based
biotech TiGenix recently gained a new partner in Sistemic, a provider of
miRNA-based products to the drug development, cell therapy and
bioprocessing
markets.

The project, called REGENER-AR, aims to progress TiGenix's
Cx611 stem
cell therapy for rheumatoid arthritis through early clinical trials.
The multidisciplinary consortium spans several countries—Belgium, Spain,
France,
the Netherlands and now the U.K.—and has been granted $7.8 million from
the European Seventh Framework Programme (FP7) under the topic "Regenerative
medicine clinical trials"
within the FP7's Health theme.

TiGenix is almost as new as the consortium itself, as the
company
merged with Cellerix, a Spanish biotech that is also focused on cell
therapies, a little more than a year ago. Since that time, the newly formed
company has been working to evaluate adipose tissue-derived stem cell (eASC)
therapies for autoimmune and inflammatory diseases like rheumatoid
arthritis
(RA).

Cx611 is an allogeneic eASC product candidate for the
treatment of rheumatoid
arthritis and is currently being investigated in a
Phase IIa trial. The trial is based on a three-step dose-finding protocol,
where each step starts
with a safety review of the first three patients after
40 days of dosing.﻿ In
February, the study opened the third and last cohort.

The study has three objectives. Its primary objective to
determine safety, feasibility and tolerance, and to identify dose-limiting
toxicity and the
dose for future clinical trials on efficacy of the intravenous
infusion of allogeneic eASCs for patients suffering rheumatoid arthritis under
treatment
with at least two non-biologic-DMARDs who have previously failed to
treatment with at least two biologics. The secondary objective is to obtain
information on the clinical and functional effects of the intravenous infusion
of allogeneic eASCs cells in patients with rheumatoid arthritis﻿,
and the third objective
is to explore pharmacodynamic parameters.

The multicenter study involves
53 patients divided into
three cohorts with different dose regimens and with the same administration regimens
and is being conducted in more than 20
Spanish centers. TiGenix expects to
report the final results of the Phase IIa in the first half of 2013. If the
results are as anticipated, TiGenix
plans to take the program forward in one or
several inflammatory and autoimmune﻿
orphan or niche indications.

"Our role will be the clinical coordination of clinical
trials within the grant, and then we will have a series of leading roles in
the
preclinical evaluation of Cx611," says Wilfried Dalemans, chief technology
officer and vice president of regulatory affairs at TiGenix. "The goal
of this project
is to progress a treatment for RA, which is a complex disease. It would be
great if we have supporting clinical data which indicate
that stem cells can
indeed be a possible treatment option for RA patients. On the preclinical side,
a more in-depth understanding of the mode of action
of stem cells in
controlling inflammation will be equally important."

The consortium has 10
partners to date, and the most recent
addition to that group is Sistemic, which will use its miRNA-based screening
platform to provide identity markers
for TiGenix's product. This miRNA-based
fingerprint will then be developed to fully characterize the product in line
with regulatory requirements and
provide a quality control (QC) tool to monitor
product quality during manufacturing scale-up for subsequent clinical trials
and aid in the selection of
manufacturing process improvements.

"Stem cells are still in the early stages of their science,
"
Dalemans notes, "and although we know they have great potential in inflammatory
control and tissues, there are still a lot of unknowns with respect
to their
origin and genealogy. One aspect of miRNAs is to focus on regulatory pathways
that can group types of regulatory pathways within cells.
Sistemic has built a
technical platform based on the scientific background of miRNAs, so they were
the partner of choice."

miRNA-based characterization provides a powerful and
informative way to identify and monitor the identity, purity, safety
and
differentiation staging of stem cells, says Vincent O'Brien, chief scientific officer
at Sistemic.

"Importantly, this approach not only gives a succinct read
out on the status of the cells, but also provides insight into the
underlying
biological effects associated with any change observed," says O'Brien. "We see
miRNAs acting as molecular beacons on the molecular status
of the cell system,
providing a much less cumbersome, more robust and biologically informative tool
to monitor cells."

miRNA-based characterization holds enormous promise for
cell-therapy product development because current methodologies are
time- and
labor-intensive and are becoming a bottleneck in progressing cell therapies
through to manufacturing, says Verna McErlane, Sistemic's
director of
commercial operations.

"Full characterization is the cornerstone to successful
development of any cell therapy and must span from early R&D through pilot
production for trials to full-scale manufacture," says McErlane. "Only
in this
way can a cell product be produced consistently and reproducibly. As a
consequence, innovative companies such as Sistemic are working on novel
methodologies, tool and products that can be used to sensitively and robustly
characterize cell therapy products. In essence, sophisticated molecular
characterization, and the ability to link this back to system biology, will be
instrumental in delivering full characterization of the cell, the
process and
the product. As with any new technology it will be important that they are
standardized for use in the industrial setting—something that
Sistemic is
developing in collaboration with its global partners."